Antibodies to CD44 enhance adhesion of normal CD34⁺ cells and acute myeloblastic but not lymphoblastic leukaemia cells to bone marrow stroma

Abstract

Summary. The role of CD44 in the adhesion of haemopoietic cells to bone marrow stromal layers has not been clearly defined in humans, although its importance in the murine system has been well documented. We have demonstrated that the CD44 antibody, NIH44-1, enhances the adhesion of haemopoietic cells to bone marrow stroma. Normal human CD34 þ haemopoietic progenitors and blasts from patients with acute myeloblastic, but not lymphoblastic, leukaemia responded to NIH44-1. All CD44 antibodies tested which bound the same epitope as NIH44-1 also augmented haemopoietic cell adhesion to bone marrow adherent layers; however, antibodies which bound to other CD44 epitopes showed mixed responses. Augmented adhesion was independent of cell metabolism, suggesting that antibody binding resulted in direct activation of the CD44 molecule. However, hyaluronic acid was not the ligand for induced adhesion, nor could we show a role for other CD44 ligands including fibronectin, laminin, collagen or chondroitin sulphate proteoglycan. Similarly, none of the 22 CD44 antibodies tested inhibited the stimulatory effect of the NIH44-1. Expression of CD44 was not sufficient to determine NIH44-1 responsiveness since cell lines and leukaemic cells which failed to respond to NIH44-1 expressed high levels of CD44. Neither CD44 isoforms nor glycosylation patterns could be identified as predictive of response. CD44 antibodies enhanced binding of normal and leukaemic haemopoietic progenitors to bone marrow fibroblasts via an unidentified stromal ligand.

Adhesion of Human Hematopoietic Progenitor Cells to Mesenchymal Stromal Cells Involves CD44

“…Our results have demonstrated that CD44 is involved in cell adhesion of the KG1a cells and of CD34+ HPC and confirmed that CD44 is localized on the uropod of CD34+ cells at the site of contact in alignment with previous studies [Giebel et al, 2004;Wagner et al, 2005a]. Other authors demonstrated that CD44 plays a major role in HPC stroma adhesion in the murine [Miyake et al, 1990] and human system [Bendall et al, 1997;Bendall and Gottlieb, 1999;Muller-Sieburg et al, 2000]. CD44 has at least 3 nonoverlapping epitopes.…”

Premature aging induced by radiation exhibits pro‐atherosclerotic effects mediated by epigenetic activation ofCD44 expression

“…Instead one of the antibodies even adhesion appears counter-intuitive, it is not unprecedented. Oostendorp et al (Oostendorp et al, 1996;Bendall et al, 1997) showed after testing a panel of nineteen anti-CD44 antibodies, that while none of them blocked hematopoietic cells from adhering to bone marrow stroma, nine of them actually enhanced binding. The majority of those that did were antibodies directed to epitope 1 of CD44, which is also the epitope recognized by the CD44 antibody (antibody 3) that exhibited the greatest enhancement of monocyte adhesion.…”

Disruption of the CXCR4/CXCL12 chemotactic interaction during hematopoietic stem cell mobilization induced by GCSF or cyclophosphamide

“…The remaining chemotactic activity after digestion of synthetic human CXCL12α was measured using CD34 + cells freshly isolated from normal human BM (26) or Nalm-6 cells as previously described (27). Cells (5 × 10 4 ) were plated in 8-µm pore transwell inserts (Corning Costar, Cambridge, Massachusetts, USA).…”